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Monday 22nd November, 2004
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Without GAPDS, glycolysis is selectively blocked in sperm
which in turn led to arrest of all progressive sperm movement.
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CHAPEL HILL -- A study led by scientists at the University of North
Carolina at Chapel Hill has determined that a novel enzyme in sperm is
essential for sperm motility and male fertility.
The new study may offer a potential target for an effective,
non-hormonal male contraceptive, the researchers said. The findings will
be published today (Nov. 15) in the online early edition of the journal
Proceedings of the National Academy of Sciences. A report also will
appear Nov. 23 in the journal's print edition.
Collaborating with UNC were scientists from the U.S. National
Institute of Environmental Health Sciences (NIEHS); Fudan University in
Shanghai, China; and the U.S. Environmental Protection Agency.
Sperm motility, produced by the coordinated movement of the extremely
long sperm tail, requires substantial energy in the form of adenosine
triphosphate, or ATP, the major energy currency of the cell. Specialized cellular structures known as mitochondria were thought to
provide a substantial portion of the ATP needed for sperm motility. In
contrast, Dr. Deborah A. O'Brien, associate professor of cell and
developmental biology at UNC's School of Medicine, and her colleagues
found that sperm motility and ATP production depend primarily on a
metabolic pathway known as glycolysis. This pathway uses sugar to
produce energy, a common process in animal and plant cells.
The researchers focused on the enzyme glyceraldehyde 3-phosphate
dehydrogenase-S, or GAPDS, a novel enzyme in the glycolytic pathway that
is expressed only in germ cells very late in the process of sperm
production. GAPDS is tightly bound to a structural element that extends along
most of the length of the sperm tail. The study team used gene
targeting, or gene knockout technology, to produce mice that could not
make this unique enzyme. Without GAPDS, glycolysis is selectively
blocked in sperm and this pathway produces no ATP. As expected, the
females were normal and the males had normal testes and sperm counts,
but they were infertile, O'Brien said.
And when the researchers analyzed sperm movement under a microscope,
they found a surprise. "We expected that a type of motility known as 'hyperactivated
motility' would be inhibited, but found that all progressive movement
was absent in sperm without GAPDS," O'Brien said. "Glycolysis may not be
as efficient as mitochondria for producing energy, but the enzymes are
abundant and in the right place for quick, localized energy production
along the sperm tail. This paper provides proof of principle that GAPDS
may be an effective target for a contraceptive agent."
Sources
SOURCES: Kubota, H. Proceedings of the National Academy of
Sciences, online edition. News release, National Institutes of
Health.
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